Several experiments have been performed to examine the hypothesis that submembrane granular fusion to cell membranes is driven by granular osmotic pressure, vesicular swelling, and membrane perforation at the point of contact between granular vesicle and cell membrane. A method has been developed to study exocytosis in vitro. Analysis of kinetic parameters reveals a simple dependence of rate of exocytosis on calcium concentration. In clear support of the hypothesis, it has been found that fusion is stopped by the application of inhibitory osmotic pressure of polymeric (dextran) solutions. Image analysis of light micrographs also shows visible granular swelling just prior to disappearance through fusion.